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A combined ultrasonic and photoacoustic imaging system is presented that is capable of deep tissue imaging. The system consists of a modified clinical ultrasound array system and tunable dye laser pumped by a Nd:YAG laser. The system is designed for noninvasive detection of sentinel lymph nodes and guidance of needle biopsies for axillary lymph node staging in breast cancer patients. Using a fraction of the American National Standards Institute (ANSI) safety limit, photoacoustic imaging of methylene blue achieved penetration depths of greater than 5 cm in chicken breast tissue. Photoacoustic imaging sensitivity was measured by varying the concentration of methylene blue dye placed at a depth of 3 cm within surrounding chicken breast tissue. Signal-to-noise ratio, noise equivalent sensitivity, and axial spatial resolution were quantified versus depth based on in vivo and chicken breast tissue experiments. The system has been demonstrated in vivo for detecting sentinel lymph nodes in rats following intradermal injection of methylene blue. These results highlight the clinical potential of photoacoustic image-guided identification and needle biopsy of sentinel lymph nodes for axillary staging in breast cancer patients.

We developed a tri-modal system combining photoacoustic (PA) tomography, thermoacoustic (TA) tomography, and ultrasound (US) imaging. Acquired images of an excised dog prostate were compared to histology results. All three modalities can image distinct features. Features like the urethra were shown in both TA and US images, but TA gave a higher contrast-to-noise ratio. Fibrous tissue was more clearly imaged by TA, while the duct structure was better shown in PA images. These experimental results demonstrate the potential advantages of our tri-modal imaging system.

Sentinel lymph node biopsy (SLNB) has become the standard method for axillary staging in breast cancer patients, relying on invasive identification of sentinel lymph nodes (SLNs) following injection of blue dye and radioactive tracers. While SLNB achieves a low false negative rate (5-10%), it is an invasive procedure requiring ionizing radiation. As an alternative to SLNB, ultrasound-guided fine needle aspiration biopsy has been tested clinically. However, ultrasound alone is unable to accurately identify which lymph nodes are sentinel. Therefore, a non-ionizing and noninvasive detection method for accurate SLN mapping is needed. In this study, we successfully imaged methylene blue dye accumulation in vivo in rat axillary lymph nodes using a Phillips iU22 ultrasound imaging system adapted for photoacoustic imaging with an Nd:YAG pumped, tunable dye laser. Photoacoustic images of rat SLNs clearly identify methylene blue dye accumulation within minutes following intradermal dye injection and co-registered photoacoustic/ultrasound images illustrate lymph node position relative to surrounding anatomy. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding chicken breast tissue on top of the rat skin surface. These results raise confidence that photoacoustic imaging can be used clinically for accurate, noninvasive SLN mapping.

Real-time temperature monitoring with high spatial resolution (~1 mm) and high temperature sensitivity (1 °C or better) is needed for the safe deposition of heat energy in surrounding healthy tissue and efficient destruction of tumor and abnormal cells during thermotherapy. A temperature sensing technique using thermoacoustic and photoacoustic measurements combined with a clinical Philips ultrasound imaging system (iU22) has been explored in this study. Using a tissue phantom, this noninvasive method has been demonstrated to have high temporal resolution and temperature sensitivity. Because both photoacoustic and thermoacoustic signal amplitudes depend on the temperature of the source object, the signal amplitudes can be used to monitor the temperature. The signal is proportional to the dimensionless Grueneisen parameter of the object, which in turn varies with the temperature of the object. A temperature sensitivity of 0.5 °C was obtained at a temporal resolution as short as 3.6 s with 50 signal averages.

The tuning curves with temperature and incidence angle for second-harmonic generation were asymmetrically distorted and broadened with increasing intensity for narrow input fundamental beams in periodically poled KTiOPO4 . Multiple phenomena including mutual self-focusing of the fundamental and harmonic, cascading, quadratic soliton generation, and artificially induced walk-off ~for light incidence away from the poling axis! contribute, in good agreement with theory., Peer Reviewed, Postprint (published version)